CRISPR to Protect the Bone Marrow & Attack Cancer: Robert Ang on The Long Run

Today’s guest on The Long Run is Robert Ang.

Robert is the CEO of Cambridge, Mass.-based Vor Bio.

Robert Ang, CEO, Vor Bio

The company is working on what I think you could call an elegant application of CRISPR gene editing for the treatment of acute myeloid leukemia.

The idea here takes some explaining but is pretty simple. Patients with acute myeloid leukemia typically get treated with adult stem cell transplants, otherwise known as bone marrow transplants. Vor seeks to make a single, important change to those transplants.

It uses CRISPR to delete the gene for making the CD33 antigen that appears on the surface of those cells.

That’s important because that marker is found on both blood-forming stem cells that reside in the bone marrow, and on the runaway malignant cancer cells in patients with AML.

The concept, from scientific founder Sid Mukherjee at Columbia University, is essentially, if you can delete CD33 from those critical blood-forming cells in the bone marrow, you can shield them from a powerful cancer drug aimed at the CD33 antigen.

Pfizer’s Mylotarg is the original antibody-drug conjugate that works this way. It has been around 20 years, but its use has been limited because of toxicity.

Vor has shown, in preliminary clinical trial results, that it can successfully delete the CD33 antigen from adult blood-forming stem cells, that these cells can engraft in the bone marrow to reconstitute a patient’s immune system, and that it’s safe. Then, importantly, in a few patients, the company has shown it can deliver the Mylotarg hammer, and that it can do its job, hitting the cancer cells that bear CD33, without damaging the newly transplanted blood-forming stem cells in the bone marrow.

This is a case where CRISPR isn’t the therapy itself for cancer, but it’s an important tool that enables us to reimagine how to better use an existing drug.

Vor isn’t stopping there. It’s developing a CD33-directed CAR-T cell therapy that could be given to these same patients. Nobody has developed such a treatment because, ordinarily, it would have been considered way too toxic to the bone marrow. But it suddenly enters the realm of the possible if you can use CRISPR to shield the bone marrow. 

I wrote about this concept, and Vor’s early clinical trial results, on Timmerman Report in November 2023.

Like many biotech entrepreneurs, Robert has taken a circuitous path. He’s an immigrant, and a physician. When that didn’t feel right for him, he explored the world of healthcare in management consulting and venture capital.

He found something here that he’s passionate about, and it shows in this conversation.

Now, please join me and Robert Ang on The Long Run.